Genetic Variant SLC10A2:c.497-74C>A (chr13-103052782-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000452.3(SLC10A2):c.497-74C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 926,222 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 59 hom., cov: 32)

Exomes 𝑓: 0.018 ( 203 hom. )

Consequence

SLC10A2
NM_000452.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.283

Publications

2 publications found

Variant links:

Genes affected

SLC10A2 (HGNC:10906): (solute carrier family 10 member 2) This gene encodes a sodium/bile acid cotransporter. This transporter is the primary mechanism for uptake of intestinal bile acids by apical cells in the distal ileum. Bile acids are the catabolic product of cholesterol metabolism, so this protein is also critical for cholesterol homeostasis. Mutations in this gene cause primary bile acid malabsorption (PBAM); muatations in this gene may also be associated with other diseases of the liver and intestines, such as familial hypertriglyceridemia (FHTG). [provided by RefSeq, Mar 2010]

SLC10A2 Gene-Disease associations (from GenCC):

bile acid malabsorption, primary, 1
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SLC10A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0246 (3741/152162) while in subpopulation AFR AF = 0.0371 (1540/41534). AF 95% confidence interval is 0.0355. There are 59 homozygotes in GnomAd4. There are 1733 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 59 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.497-74C>A		intron_variant	Intron 2 of 5	ENST00000245312.5	NP_000443.2	Q12908

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5 link	c.497-74C>A		intron_variant	Intron 2 of 5	1	NM_000452.3	ENSP00000245312.3		Q12908

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3741

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0371

Gnomad AMI

AF:

0.0516

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.0734

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0230

GnomAD4 exome

AF:

0.0183

AC:

14171

AN:

774060

Hom.:

203

AF XY:

0.0180

AC XY:

7400

AN XY:

411432

show subpopulations

African (AFR)

AF:

0.0393

AC:

783

AN:

19900

American (AMR)

AF:

0.00931

AC:

389

AN:

41762

Ashkenazi Jewish (ASJ)

AF:

0.0668

AC:

1450

AN:

21712

East Asian (EAS)

AF:

0.0000276

AC:

AN:

36202

South Asian (SAS)

AF:

0.00455

AC:

326

AN:

71688

European-Finnish (FIN)

AF:

0.0117

AC:

598

AN:

51144

Middle Eastern (MID)

AF:

0.0356

AC:

157

AN:

4406

European-Non Finnish (NFE)

AF:

0.0197

AC:

9632

AN:

489534

Other (OTH)

AF:

0.0221

AC:

835

AN:

37712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

740

1480

2221

2961

3701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0246

AC:

3741

AN:

152162

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1733

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0371

AC:

1540

AN:

41534

American (AMR)

AF:

0.0128

AC:

196

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0734

AC:

255

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00333

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0119

AC:

126

AN:

10590

Middle Eastern (MID)

AF:

0.0514

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0220

AC:

1498

AN:

67994

Other (OTH)

AF:

0.0227

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

181

363

544

726

907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0251

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

(source)

DANN

Benign

0.33

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over